A Single Oral Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO6836191 in Healthy Male Subjects Including a Single Intravenous Microdose of RO6836191
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 88
- Primary Endpoint
- Part 2: Urine aldosterone levels
Study Overview
Brief Summary
This single-center, randomized, placebo-controlled, double-blind study will assess the safety, pharmacokinetics and pharmacodynamics of RO6836191 in healthy male volunteers in two parts. Part 1 will assess the safety of oral single ascending doses of RO6836191 compared to placebo in fasted volunteers. In Part 2, participants will be given two single oral doses of RO6836191 or placebo under low or normal-salt diet conditions. A subset of these participants will subsequently receive a single IV dose of RO6836191 for further analysis.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy male volunteers, aged 18 to 45 years old.
- •No active or chronic disease following a detailed medical and surgical history and complete physical examination.
- •A BMI between 18 to 30 kg/m2 inclusive.
- •Use of a highly effective form of birth control for the duration of the study and until 90 days after the last dose.
Exclusion Criteria
- •Any clinically relevant current or history of conditions or illnesses.
- •Clinically significant symptoms of infection within 5 days of the first dosing day or a history of recurrent infections.
- •Any suspicion or history of alcohol abuse and/or consumption of other drugs of abuse.
- •Smokers unable or unwilling to restrict to 5 cigarettes daily during the study and to not smoke during the stay at the clinic.
- •Any cardiac abnormalities.
- •Blood donation over 450 mL within three months prior to screening.
- •Participation in an investigational drug or device study within 3 months prior to dosing.
- •Corticosteroid use within 3 months prior to dosing.
Arms & Interventions
Part 2: RO6836191: NS followed by LS diet
Intervention: NS followed by LS diet condition (Other)
Part 2: RO6836191: NS followed by LS diet
Intervention: RO6836191 (Drug)
Part 1: Single Ascending Doses (SAD) of RO6836191
Intervention: RO6836191 (Drug)
Part 1: Placebo (PL)
Intervention: Placebo (Drug)
Part 2: PL: Low-salt (LS) followed by normal-salt (NS) diet
Intervention: LS followed by NS diet condition (Other)
Part 2: PL: Low-salt (LS) followed by normal-salt (NS) diet
Intervention: Placebo (Drug)
Part 2: PL: Low-salt (LS) followed by normal-salt (NS) diet
Intervention: RO6836191 (Drug)
Part 2: PL: NS followed by LS diet
Intervention: NS followed by LS diet condition (Other)
Part 2: PL: NS followed by LS diet
Intervention: Placebo (Drug)
Part 2: PL: NS followed by LS diet
Intervention: RO6836191 (Drug)
Part 2: RO6836191: LS followed by NS diet
Intervention: LS followed by NS diet condition (Other)
Part 2: RO6836191: LS followed by NS diet
Intervention: RO6836191 (Drug)
Outcomes
Primary Outcomes
Part 2: Urine aldosterone levels
Time Frame: Up to 3 days after drug administration
Part 1: Plasma aldosterone levels
Time Frame: Up to Day 5
Part 2: Incidence of AEs
Time Frame: Up to 12 weeks
Parts 1: Incidence of adverse events (AE)
Time Frame: Until Day 21
Part 1: Urine aldosterone levels
Time Frame: Up to Day 3
Part 2: Area under the concentration-time curve (AUC)
Time Frame: Up to Day 35
Part 2: Plasma aldosterone levels
Time Frame: Up to 2 days after drug administration
Secondary Outcomes
- Part 2: Volume of distribution after intravenous administration(Days 28-37)